We propose the study of renal function with the help of a new analytical approach, electronprobe microanalysis, which improves standard micropuncture procedures and makes the analysis of the ionic content of tubular epithelial cells possible. Electronprobe microanalysis provides: 1) the ability to analyse "ideal" sampling fluid from the tubule, i.e., volumes of 20 picoliters or less instead of nanoliters; 2) the ability to perform, on the same picoliter samples, quantitative analysis of any element of atomic number higher than fluorine (e.g., Mg, Na, Ca, P, K, Cl, S); and 3) the possibility of analysing organic components with a microprecipitation procedure we have just developed. The Biotechnology Resource in Electron Probe Microanalysis, which permits these studies, has been funded and is now established. Our aims are micropuncture studies of sulfate excretion, ionic composition of peritubular blood, bicarbonate movements, and anion excretion in parathyroidectomized animals under parathormone and calcitonin. A countercurrent model will rely on the countercurrent concentration profile as quantitatively measured from the cortex to the papilla in different diuretic states using sodium ferrocyanide. We will extend micropuncture to the study of ionic composition of the entire population of nephrons by microdissecting frozen pieces of tubular fluid within frozen kidney slices. We will compare the tubular fluid composition to the tubule epithelial cells by characteristic X-ray scanning for elements of interest (Na, K, Cl, Mg, S, P).